Hajime Togari

Nagoya City University, Nagoya, Aichi, Japan

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Publications (187)500.7 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim To examine whether Cycrobilirubin Formation Capacity (CFC) could be clinically relevant in the treatment of neonatal hyperbilirubinemia. Study design CFC is a sum of irradiances multiplied by the wavelength-specific bilirubin photoisomerization rate, calculated at 40 nm intervals between the ranges 400–520 nm, measured using a novel spectroradiometer. After evaluating CFC and footprints of light emitting diode (LED) device and fluorescent tube (FT) device, we performed a randomised controlled trial (RCT) to test whether phototherapies provided with different light spectra using the same CFC are equally effective. Thirty-two babies were enrolled without any exclusion criteria. Total serum bilirubin (TSB) levels before and after phototherapies were compared. Result Seventeen babies were assigned to FT and fifteen to LED group. Birth characteristics were similar. Changes in TSB levels before and after phototherapy in LED and FT group were not different. Conclusion Under the same CFC evaluated by the spectroradiometer, LED was as effective as FT. This supports the idea that CFC could be relevant in phototherapy for the treatment of hyperbilirubinemia in otherwise healthy newborns.
    No preview · Article · Oct 2014 · Archives of Disease in Childhood
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    Full-text · Dataset · Sep 2014
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    Full-text · Article · Jan 2014
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    ABSTRACT: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare leukoencephalopathy first described by van der Knaap in 2002. Diffuse cerebral hypomyelination and atrophy of the basal ganglia and cerebellum characterize H-ABC. We report a 9-year-old Japanese boy with H-ABC who had been suspected to have Pelizaeus Merzbacher disease. Brain MRI revealed delayed myelination, however, no other remarkable abnormal laboratory findings were found. PLP1 gene mutation was not detected and he had no nystagmus. He was diagnosed as having H-ABC at the age of 8 years because of supratentorial hypomyelination and progressive atrophy of the basal ganglia and cerebellum on the follow-up MRI. This boy's condition was clinically more severe than those with other reported patients with H-ABC.
    No preview · Article · Jul 2013 · No to hattatsu. Brain and development
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    ABSTRACT: Background: Main indications for liver transplantation in the pediatric population include biliary atresia and inherited metabolic diseases. The present study evaluated whether there are differences between pediatric patients undergoing living-related liver transplantation due to the two diseases in terms of their oxidative and immunological status during their regular outpatient follow-up visits. Material and methods: A clinical outpatient study measuring serum oxidative stress index (calculated as serum oxidant/antioxidant ratio, in the form of serum total hydroperoxide/serum biological antioxidative potential), serum terminal complement component 5a, as an indicator of complement activity and immunological status, and transforming growth factor-ß1, as a marker of liver fibrosis, in 16 patients (6 males and 10 females, 2.5-15 years old) who received living-related liver transplantation due to inherited metabolic diseases (n=6; in the form of propionic acidemia [n=1], methylmalonic acidemia [n=1], arginase deficiency [n=1], tyrosinemia [n=2], and glycogen storage disease type 1b [n=1], with an age range of 2.4-14.6 years old) and due to biliary atresia ([n=10], with an age range of 2.9-14.5 years old). Results: Serum oxidative stress index, complement component-5a, and transforming growth factor-ß1 were significantly higher in the inherited metabolic diseases group than in the biliary atresia group. In all patients, serum oxidative stress index correlated positively with complement component-5a and transforming growth factor-ß1. Conclusions: Patients who receive living-related liver transplantation due to inherited metabolic diseases are prone to higher oxidative stress, complement activity, and serum transforming growth factor-ß1.
    Full-text · Article · Feb 2013
  • S Kato · T Sugiura · H Ueda · K Ito · H Kakita · I Kato · K Kawabata · H Ohto · H Togari
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    ABSTRACT: Neonatal alloimmune thrombocytopenia (NAIT) is a rare but clinically important etiology of intracranial hemorrhage. There have been no reported cases of intracranial hemorrhage caused by anti-group A or anti-group B antibodies. A Japanese boy weighing 1550 g was born at 37 weeks. He suffered from refractory thrombocytopenia and developed severe intracranial hemorrhage on his second day. Despite repeated platelet, red-cell and fresh-frozen-plasma transfusions, he died at day 10 of life. Serological studies and genotyping of the patient and his parents were performed. There were no incompatible genotypes of platelet antigens between the patient and the mother. Serological studies revealed that the mother had extremely high-titer anti-group A immunoglobulin G(2) (4096-fold) that reacted strongly with the father's platelets. The reaction against the father's platelets disappeared when her serum was adsorbed with group A red blood cells. Maternal anti-group A antibody was associated with NAIT and severe bilateral intracranial hemorrhage.
    No preview · Article · Jan 2013 · Journal of perinatology: official journal of the California Perinatal Association
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    ABSTRACT: To study the effect of exchange transfusion on cytokine profiles in a patient with necrotizing enterocolitis, the levels of 12 cytokines and serum calprotectin were measured among exchange transfusion. A male extremely low birth weight infant was in non-compensated shock and diagnosed stage 3 necrotizing enterocolitis. Exchange transfusion was performed for critical condition, refractory hypotension and disseminated intravascular coagulation. After exchange transfusion, the patient's blood pressure increased and stabilized. Then an enterostomy was performed and revealed necrosis of the ascending colon. Of the cytokines examined, interleukin-8 and serum calprotectin were high before exchange transfusion and decreased after exchange transfusion.
    No preview · Article · Dec 2012 · Pediatrics International
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    ABSTRACT: Background: Oxidative stress (oxidant-antioxidant imbalance) plays an important role in the pathophysiology of neonatal sepsis. This study evaluated whether an antisense peptide endothelin receptor antagonist, ETR-P1/fl, could attenuate oxidative stress in a neonatal sepsis model. Methods: A total of 18 3-d-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05 mg/kg/h) of ETR-P1/fl 30 min after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAPs), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT), and creatinine were measured before CLP and at 1, 3, and 6 h after CLP. Results: CLP evoked a state of shock resulting in elevated TH, OSI, and IL-6 levels. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3 h after CLP, OSI at 1 and 3 h after CLP, IL-6 at 1 and 3 h after CLP, and GOT at 3 and 6 h after CLP as compared with the CLP group. Conclusion: ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6, and GOT in a progressive neonatal sepsis CLP model.
    Full-text · Article · Oct 2012 · Pediatric Research
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    ABSTRACT: Perinatal hypoxia-ischemia (HI) frequently causes white-matter injury, leading to severe neurological deficits and mortality, and only limited therapeutic options exist. The white matter of animal models and human patients with HI-induced brain injury contains increased numbers of oligodendrocyte progenitor cells (OPCs). However, the origin and fates of these OPCs and their potential to repair injured white matter remain unclear. Here, using cell-type- and region-specific genetic labeling methods in a mouse HI model, we characterized the Olig2-expressing OPCs. We found that after HI, Olig2+ cells increased in the posterior part of the subventricular zone (pSVZ) and migrated into the injured white matter. However, their oligodendrocytic differentiation efficiency was severely compromised compared with the OPCs in normal tissue, indicating the need for an intervention to promote their differentiation. Erythropoietin (EPO) treatment is a promising candidate, but it has detrimental effects that preclude its clinical use for brain injury. We found that long-term postinjury treatment with a nonerythropoietic derivative of EPO, asialo-erythropoietin, promoted the maturation of pSVZ-derived OPCs and the recovery of neurological function, without affecting hematopoiesis. These results demonstrate the limitation and potential of endogenous OPCs in the pSVZ as a therapeutic target for treating neonatal white-matter injury. STEM Cells2012;30:2234-2247.
    No preview · Article · Oct 2012 · Stem Cells
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    ABSTRACT: Periventricular leukomalacia is recognized as the leading cause of cerebral palsy in preterm infants. To clarify the prevalence of periventricular leukomalacia and cerebral palsy in Japan, a nationwide survey was performed. The prevalence of periventricular leukomalacia in the group of surviving preterm infants of gestational ages less than 33 weeks born in 2007 was 2.7% (78/2883) on ultrasound diagnosis, and 3.3% (92/2824) on magnetic resonance imaging. The prevalence of cerebral palsy was 4.3% (125/2883) on clinical diagnosis. In our previous study, the prevalences of periventricular leukomalacia in 1990-1991, 1993-1994, 1996, and 1999 were 4.8%, 4.9%, 4.9%, and 5.3% on ultrasound, and 7.9%, 7.7%, 6.9%, and 7.3% on magnetic resonance imaging, respectively. The prevalence of periventricular leukomalacia has decreased significantly in Japan.
    No preview · Article · Jul 2012 · Pediatric Neurology
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    ABSTRACT: This retrospective case-control study aimed to examine the development of oxidative stress in asphyxiated infants delivered at more than 37 weeks of gestation. Thirty-seven neonates were stratified into 3 groups: the first group experienced hypothermia (n = 6); the second received hypothermia cooling cup treatment for 3 days, normothermia (n = 16); and the third was the control group (n = 15). Serum total hydroperoxide (TH), biological antioxidant potential, and oxidative stress index (OSI) (calculated as TH/biological antioxidant potential) were measured within 3 hours after birth. Serum TH and OSI levels gradually increased after birth in hypothermia and normothermia cases. At all time points, serum TH and OSI levels were higher in hypothermia and normothermia cases than in control cases. Serum TH and OSI levels were higher in normothermia cases than in hypothermia cases at days 3, 5, and 7. This study demonstrated that hypothermia attenuated the development of systemic oxidative stress in asphyxiated newborns.
    No preview · Article · Feb 2012 · Journal of critical care

  • No preview · Article · Feb 2012 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: To investigate the long-term efficacy and safety of two doses (33 and 67 μg/kg/day) of growth hormone (GH) in short Japanese children born small for gestational age (SGA). 96 children born SGA (age 3 to <8 years) were randomized to GH at 33 or 67 μg/kg/day for 104 weeks, or to an untreated control (UC) group for 52 weeks. After 52 weeks, the UC group was randomized to GH at a dose of 33 or 67 μg/kg/day for a 156-week extension study. Initial treatment groups continued unchanged for the extension phase. Efficacy was evaluated by change in height SDS for chronological age from baseline to 208/260 weeks. After 208 weeks, change in height SDS from baseline (least square (LS) means (SE)) was 1.01 (0.47) and 1.99 (0.67) in the UC 33 and UC 67 μg/kg/day groups, respectively. After 260 weeks, change in height SDS from baseline was 1.22 (0.51) and 2.01 (0.64) in the 33 and 67 μg/kg/day groups, respectively. Insulin-like growth factor-1 levels were significantly higher in the groups receiving 67 μg/kg/day but largely remained within normal limits (-2 to +2 SDS). Long-term continuous GH treatment was well tolerated and effective in improving height SDS. Improvements were dose-dependent and significantly higher at 67 than 33 μg/kg/day.
    Full-text · Article · Nov 2011 · Hormone Research in Paediatrics
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    ABSTRACT: Vitamin B12 deficiency in infants often presents with nonspecific hematological, gastrointestinal, and neurological manifestations. It is usually caused by inadequate intake, abnormal absorption, or congenital disorders of vitamin B12 metabolism, including transport disorders. We describe a vitamin B12-deficient infant with severe anemia who was breastfed. His mother had undiagnosed vitamin B12 deficiency having undergone total gastrectomy 18 years earlier. The infant developed normally after taking vitamin B12. It is important to suspect vitamin B12 deficiency in mothers who have undergone gastrectomy. Early diagnosis and treatment of vitamin B12 deficiency in infants is important and will help improve long-term prognosis.
    No preview · Article · Oct 2011 · Journal of Pediatric Hematology/Oncology
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    ABSTRACT: The hypoxia-responsive cytokine erythropoietin (EPO) provides neuroprotective effects in the damaged brain during ischemic events and neurodegenerative diseases. The purpose of the present study is to evaluate the EPO/EPO receptor (EPOR) endogenous system between astrocyte and oligodendrocyte precursor cell (OPC) under hypoxia. We report here elevated EPO mRNA levels and protein release in cultured astrocytes following hypoxic stimulation by quantitative RT-PCR and ELISA. Furthermore, the EPOR gene expressions were detected in cultured OPCs as in astrocytes and microglias by quantitative RT-PCR. Cell staining revealed the EPOR expression in OPC. To evaluate the protective effect of endogenous EPO from astrocyte to OPCs, EPO/EPOR signaling was blocked by EPO siRNA or EPOR siRNA gene silencing in in vitro study. The suppression of endogenous EPO production in astrocytes by EPO siRNA decreased the protection to OPCs against hypoxic stress. Furthermore, OPC with EPOR siRNA had less cell survival after hypoxic/reoxygenation injury. This suggested that EPO/EPOR signaling from astrocyte to OPC could prevent OPC damage under hypoxic/reoxygenation condition. Our present finding of an interaction between astrocytes and OPCs may lead to a new therapeutic approach to OPCs for use against cellular stress and injury.
    No preview · Article · Oct 2011 · Journal of Neuroscience Research
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    ABSTRACT: Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.
    No preview · Article · Apr 2011 · The Tohoku Journal of Experimental Medicine
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    ABSTRACT: Oxidative stress has been suspected to influence graft survival and prognosis in pediatric recipients of living related liver transplantation (LRLT). We determined the oxidative status of pediatric LRLT recipients during their regular outpatient follow-up visits, and looked for a relationship between oxidative status and post-liver transplantation (post-LTx) duration. The study included 43 patients (20 males and 23 females) between the ages of 1.6 and 25.1 years (median 10.7 years) who had undergone LRLT from 5 months to 17.5 years (median 7 years) prior to the study, between the ages of 1.2 and 14.4 years (median 3.5 years). Serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), gamma-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), direct bilirubin and choline-esterase were measured as part of the patients' regular follow-up visits. Serum total hydroperoxide (TH) and biological antioxidative potential (BAP) were measured using the free radical analytic system which requires 20 μl of serum and 10 min of processing time for each sample. Oxidative stress index (OSI) was calculated as the ratio of TH to BAP. Serum OSI correlated positively with serum levels of GOT, GPT, LDH, ALP, γ-GTP and direct bilirubin. Serum OSI, TH, LDH, ALP and GOT correlated negatively with post-LTx duration. Serum BAP correlated positively with post-LTx duration. Serum TH correlated positively with serum GOT and γ-GTP, but negatively with serum BAP. (1) The OSI, which can be calculated based on data acquired through a simple outpatient procedure, can serve as an index of our patients' laboratory results and oxidative status. (2) The LRLT recipients in our study were at risk for oxidative stress early in the post-operative period, but this risk subsided with time.
    No preview · Article · Jan 2011 · Pediatric Surgery International

  • No preview · Article · Dec 2010 · Neuroscience Research
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    ABSTRACT: To evaluate effects of endothelin receptor antagonist ETR-P1/fl in a neonatal sepsis model. Eighteen anesthetized and mechanically ventilated 3-day-old piglets were divided into three groups. Six piglets received cecal ligation and perforation (CLP group). Six piglets were administrated a continuous infusion of ETR-P1/fl (0.05 mg/kg/h), an antisense homology box-derived peptide with an endothelin A receptor antagonist effect, starting 30 min after CLP (ETR-P1/fl group). Six piglets acted as the sham group. Mean arterial pressure (MAP), heart rate, cardiac output, arterial blood gas, body temp (BT), serum nitrite and nitrate (NOx), tumor necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB-1) were measured before CLP and at 1, 3, 6, and 9 h after CLP. Cecal ligation and perforation exposure evoked a state of shock and showed deteriorated cardiac output, pulmonary hypertension, decreased MAP, low oxygen saturation, and base excess (BE) with elevated TNF-α, NOx, and HMGB1. ETR-P1/fl administration resulted in higher MAP at 6 and 9 h after CLP, less negative BE, lower mean pulmonary arterial pressure (mPAP)/MAP ratio at 9 h after CLP, and lower TNF-α, NOx, and HMGB-1 compared to the CLP group. BT showed no differences between the groups. Survival time in the ETR-P1/fl group was longer than in the CLP group (18.9 ± 2.3 h vs. 9.0 ± 0.8 h, p < 0.01). ETR-P1/fl treatment significantly attenuated the elevation of NOx, TNF-α, and HMGB-1, which improved the systemic hypotension, pulmonary hypertension, and blood gases, thereby causing improvement of survival time in a progressive neonatal sepsis CLP model.
    No preview · Article · Dec 2010 · Intensive Care Medicine
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    ABSTRACT: Valproate (VPA) is a simple fatty acid and a substrate for the fatty acid β-oxidation pathway. Previous data suggested that the toxicity of VPA may be provoked by carnitine deficiency and the inhibition of mitochondrial β-oxidation. The aim of the present study was to elucidate the effect of VPA treatment on carnitine and isomer-differentiated acylcarnitine disposition, and determined the relationships between acylcarnitines and blood VPA levels in long-term treated patients with VPA and/or other antiepileptic drugs. Serum samples were obtained from children aged 1-15 years old treated for at least 6 months with VPA alone (n=28) or VPA combined with other anticonvulsants (n=23) and untreated controls (n=23). Serum acylcarnitines were separated from their isomers and quantified using high-performance liquid chromatography-tandem mass spectrometry. We found higher 3-hydroxyisovalerylcarnitine levels and trace amounts of valproylcarnitine in both VPA monotherapy and polytherapy patients. Other acylcarnitines, hexanoylcarnitine, C12, C14:1-carnitines and the ratio of long-chain acylcarnitine to free carnitine were also higher in VPA polytherapy individuals than in controls. VPA monotherapy does not result in decreases in free carnitine or in the accumulation of long-chain acylcarnitines. Blood VPA concentrations correlated positively with hexanoylcarnitine, C12, C14:1, C16:1, C18:1-carnitines in all VPA-treated children (n=51). Long-term VPA treatment in pediatric patients could affect some specific acylcarnitines, which is enhanced by the concomitant use of other anticonvulsants, and the formation of valproylcarnitine alone seems insufficient to develop severe carnitine deficiency at therapeutic doses of VPA.
    No preview · Article · Dec 2010 · Brain & development

Publication Stats

2k Citations
500.70 Total Impact Points


  • 1980-2013
    • Nagoya City University
      • • Department of Neonatology and Pediatrics
      • • Graduate School of Medical Sciences
      • • Department of Pediatrics
      • • Medical School
      Nagoya, Aichi, Japan
  • 2006
    • The Jikei University School of Medicine
      Edo, Tokyo, Japan
  • 2001-2004
    • Hôpital Universitaire des Enfants Reine Fabiola
      Bruxelles, Brussels Capital, Belgium
  • 2002
    • Yamagata University
      • Third Department of Internal Medicine
      Ямагата, Yamagata, Japan
  • 1986
    • Gunma Children's Medical Center
      Shibukawa, Gunma, Japan